U.S. Pat. No. 3,888,977, issued on June 10, 1975 to Murray J. Sanders (the entire disclosure of which is incorporated herein by reference and relied upon for details of disclosure) teaches that animals, including humans, may be treated for progressive degenerative neurological diseases, such as amyotropic lateral sclerosis, by administration of a modified snake venom neurotoxin derived from the venom of either the Bungarus genus (including the Crotalus genus) or from a combination of the Bungarus genus and the Naja genus, i.e. in either case the therapeutic composition must contain at least in part modified neurotoxin derived from the Bungarus genus.
As explained in that patent, degenerative neurological diseases progress in a chronic manner to severe physical disability, such as paralysis, and even to death. It is believed that many of those neurological diseases result from specific infections, e.g. viral infections or invasion by proteins with potentially deleterious functions. It is further believed that these noxious effects are caused by the virus or protein attaching to or functioning in conjunction with nerve cell receptors. These nerve cell receptors may be discrete anatomical structures or they may merely be theoretical biophysical concepts which describe one of the functions of the nerve cells. Irrespective of the theory, it is known that nerve cells do function as if physical receptors exist.
Injected neurotropic snake venom reaches a broad spectrum of nerve cell receptors in animals because of its neurotropic character. The Sanders patent teaches that such venom may retain that neurotropic character even when detoxified. Thus, by treating patients suffering from degenerative neurological diseases with detoxified neurotropic snake venom, the nerve cell receptors can be blocked by the detoxified venom and this prevents the further noxious effects of the invading pathogenic bacteria, virus or protein.
Thus, the modified neurotoxin of the Sanders patent must retain the neurotropic character of the snake venom and yet be detoxified, since the usual required dosage would be far more than sufficient to kill the patient if the venom remained in the toxic form. However, if the detoxification procedure is too harsh or is continued too long, degradation of the neurotropic character of the detoxified snake venom occurs and the therapeutic effect of the modified neurotoxin is substantially reduced or eventually entirely lost. On the other hand, if the detoxification procedure is not carried to the point of atoxicity, there always remains the possibility of a toxic reaction on the part of a recipient of the incompletely detoxified snake venom.
The Sanders patent discloses earlier work of the inventor using modified neurotoxins derived from the Naja (cobra) venom alone and that substantial benefits were provided by this earlier modified neurotoxin. However, that patent also discloses that the modified neurotoxin derived from Naja venom is not capable of completely halting the advancement of the neurological diseases, as opposed to the results with the Bungarus containing composition of the patent. Further, and of most importance, the modified neurotoxin prepared from the Naja venom alone could not be completely detoxified, since the potency and desired therapeutic effect were thought to be thereby lost. Thus, a bioassay could never show complete detoxification and there always remained a risk in the administration of the composition which was not fully detoxified.
To avoid this difficulty with the earlier modified neurotoxin, the Sanders patent discloses that the modified neurotoxin must be derived from a broad penetration venom, i.e. from the genus Bungarus (including the genus Crotalus). While the Bungarus venom is similar to the Naja venom, the venoms differ with regard to the intensity and sites of action of the physiological effect and with regard to the time required for the physiological effect. The Sanders patent discloses, however, that Naja venom may be used when combined with the Bungarus venom and indeed the combination of Bungarus venom and Naja venom gives superior results as compared with the Bungarus venom alone. Thus, it is taught that while the Bungarus venom can be effectively used alone, the Naja venom must be used in combination with the Bungarus venom.
Unfortunately, however, Bungarus venom is not as readily available as Naja venom; the supply thereof is more uncertain; and it is far more expensive than the Naja venom. It would, therefore, be of considerable benefit to the art if Naja venom could be adapted as at least an adequate modified neurotoxin according to the Sanders patent. This would insure a supply of at least an adequate therapeutic agent and at a substantial savings in cost.